Long-term depression induced by sensory deprivation during cortical map plasticity in vivo

Cortical map plasticity is thought to involve long-term depression (LTD) of cortical synapses, but direct evidence for LTD during plasticity or learning in vivo is lacking. One putative role for LTD is in the reduction of cortical responsiveness to behaviorally irrelevant or unused sensory stimuli, a common feature of map plasticity. Here we show that whisker deprivation, a manipulation that drives map plasticity in rat somatosensory cortex (S1), induces detectable LTD-like depression at intracortical excitatory synapses between cortical layer 4 (L4) and L2/3 pyramidal neurons. This synaptic depression occluded further LTD, enhanced LTP, was column specific, and was driven in part by competition between active and inactive whiskers. The synaptic locus of LTD and these properties suggest that LTD underlies the reduction of cortical responses to deprived whiskers, a major component of S1 map plasticity.     

Sleep does not enhance the recovery of deprived eye responses in developing visual cortex

Monocular deprivation (MD) during a critical period of visual development triggers a rapid remodeling of cortical responses in favor of the open eye. We have previously shown that this process is enhanced by sleep and is inhibited when the sleeping cortex is reversibly inactivated. A related but distinct form of cortical plasticity is evoked when the originally deprived eye (ODE) is reopened, and the non-deprived eye is closed during the critical period (reverse monocular deprivation (RMD)). Recent studies suggest that different mechanisms regulate the initial loss of deprived eye responses following MD and the recovery of deprived eye responses following RMD. In this study we investigated whether sleep also enhances RMD plasticity in critical period cats. Using polysomnography combined with microelectrode recordings and intrinsic signal optical imaging in visual cortex we show that sleep does not enhance the recovery of ODE responses following RMD. These findings add to the growing evidence that different forms of plasticity in vivo are regulated by distinct mechanisms and that sleep has divergent roles upon different types of experience-dependent cortical plasticity.     

Nerve growth factor favours long-term depression over long-term potentiation in layer II–III neurones of rat visual cortex

Nerve growth factor (NGF) has been shown to regulate plasticity in the visual cortex of monocularly deprived animals. However, to date, few attempts have been made to investigate the role of NGF in synaptic plasticity at the cellular level. In the study reported here we looked at the effects of exogenously applied NGF on synaptic plasticity of layer II–III regular spiking (RS) neurones in visual cortex of 16- to 18-day-old rats. We found that local application of NGF converted high frequency stimulation (HFS)-induced long-term potentiation (LTP) into long-term depression (LTD). We showed that this shift of synaptic plasticity was also obtained with bath application of NGF during HFS. Application of NGF subsequent to HFS left LTP unaffected, conferring temporal constraints on NGF efficacy. NGF effects on LTP were mediated by TrkA receptors. Indeed, blockade of TrkA by monoclonal antibody prevented NGF from inducing LTD following HFS. Low frequency stimulation (LFS) elicited LTD in RS cells. We found that NGF or blockade of NGF signalling by anti-TrkA antibody did not change the amplitude of the LTD induced by LFS. Thus, the NGF effect is selective for synaptic modifications induced by HFS in RS cells. The present results indicate that NGF may modulate the sign of long-term changes of synaptic efficacy in response to high frequency inputs.     

Lesions of nonvisual inputs affect plasticity, norepinephrine content, and acetylcholine content of visual cortex

1. The depletion of both norepinephrine (NE) and acetylcholine (ACh) in the visual cortex can decrease plasticity. This decrease in plasticity, although dramatic under some circumstances, fails to occur under others. 2. We depleted cortical NE and ACh in 35- to 42-day-old kittens by making a lesion of the white matter behind the cingulate gyrus. One eye was sutured on the day of the lesion. We recorded from the visual cortex 7 days or 2-3 mo later and used the influence of the deprived eye on the cortical cells as a measure of plasticity. 3. We measured NE content by high-pressure liquid chromatography (HPLC) and inferred ACh depletion from depletion of choline acetyltransferase (ChAT) activity. NE depletion averaged 60% in the successfully depleted animals. Depletion of ChAT activity was consistent with NE depletion. 4. When recording occurred 7 days after the lesion and the sutured eye was contralateral to the lesion, plasticity was decreased on the side with the lesion; 70% of the cells were driven by the deprived eye. On the control, uninjured side only 15% of the cells were driven by the deprived eye. 5. In two circumstances the lesion did not cause a decrease in plasticity. In animals with suture ipsilateral to the lesion, the cortex remained plastic. In these animals only 26% of the cells in the hemisphere with the lesion were driven by the deprived eye. The cortex also retained its plasticity if the contralateral eye remained sutured for several months after the lesion, even though there was no recovery from NE and ACh depletion. 6. We conclude that depletion of NE and ACh does decrease plasticity; that is, it protects the deprived eye from losing its ability to drive cortical cells, at least for a short period of time. Depletion protects only the normally dominant contralateral pathway; the ipsilateral visual pathway remains plastic. 7. Perhaps the importance of the side of the deprived eye can be explained by assuming that depletion of NE and ACh removes facilitatory input. This would decrease the ability of cortical cells on the side with lesion to potentiate the input from the nondeprived eye relative to the deprived eye; that is, it would decrease the molecular deprivation (MD) effect. A removal of facilitation would also increase the visual input required to drive cells.(ABSTRACT TRUNCATED AT 400 WORDS)     

Reactivation of visual cortical plasticity by NEP1-40 from early monocular deprivation in adult rats

Amblyopia is difficult to cure in adult due to the declination of visual cortical plasticity with age. However, the mechanisms limiting adult cortical plasticity are still unclear. Inhibition factors associated with myelin are suggested to be crucial for the ocular dominance plasticity in the visual cortex. We hypothesize that blocking Nogo-NgR system with NEP1–40 in adult visual cortex will reactivate the structural and functional plasticity. To back up this hypothesis, we subjected postnatal day 21 (P21) rats to monocular deprivation (MD) model until P45. Then the deprived eyes of MD model rats were reopened and followed by NEP1–40 or PBS administration for 7 days. Dendritic spine densities, ultrastructral modifications of synaptic junctions and objective visual function were examined at P52 to determine the therapeutic effects of NEP1–40. Our findings suggest a new curative role for NEP1–40 in structural and functional recovery from the deficits of adult MD rats, and offer a potential therapeutic tool for curing amblyopia and other cortically based visual disorders.     

Rapid eye movement sleep deprivation in post-critical period, adolescent rats alters the balance between inhibitory and excitatory mechanisms in visual cortex

Suppression of rapid eye movement sleep (REMS) in developing animals has both anatomical and physiological consequences. We have recently shown that initiating REMS deprivation (REMSD) prior to the end of the critical period in young rats delays termination of the critical period (CP) in visual cortex, and, consequently, the synaptic plasticity mechanisms that support a developmentally regulated form of long-term potentiation (LTP) are maintained in an immature state [J.P. Shaffery, C.M. Sinton, G. Bisset, H.P. Roffwarg, G.A. Marks, Rapid eye movement sleep deprivation modifies expression of long-term potentiation in visual cortex of immature rats, Neuroscience, 110 (2002) 431-443]. In CP animals, high-frequency, theta burst stimulation (TBS) directed at the white matter (WM) below visual cortex produces LTP in the post-synaptic cells in layer II/III (LTPWM-III). However, LTPWM-III can be induced in cortical tissue taken from REMS-deprived animals for up to a week beyond the usual end of the CP [J.P. Shaffery, C.M. Sinton, G. Bisset, H.P. Roffwarg, G.A. Marks, Rapid eye movement sleep deprivation modifies expression of long-term potentiation in visual cortex of immature rats, Neuroscience, 110 (2002) 431-443]. Further, in post-CP, adolescent animals (as late as postnatal day 60), REMSD appears to unmask synaptic plasticity mechanisms that allow for production of developmentally regulated LTPWM-III [J.P. Shaffery, J. Lopez, G. Bissette, H.P. Roffwarg, Rapid eye movement sleep deprivation revives a form of developmentally regulated synaptic plasticity in the visual cortex of post-critical period rats, Neurosci Lett., (2005), in press]. It has been proposed that REMSD's effects on production of LTPWM-III result from a reduction in efficiency of the inhibitory mechanisms thought to precipitate termination of the CP of brain development [J.P. Shaffery, J. Lopez, G. Bissette, H.P. Roffwarg, Rapid eye movement sleep deprivation revives a form of developmentally regulated synaptic plasticity in the visual cortex of post-critical period rats, Neurosci Lett., (2005), in press]. In this study we tested the hypothesis that low-frequency stimulation (LFS) of the fibers of the WM, which usually produces the related form of synaptic plasticity, long-term depression (LTD), will also reflect the reduction in inhibitory tone. We report here that LFS protocols, which in normally sleeping, adolescent rats usually produce either LTD or no change in response magnitude, in REMS-deprived, adolescent rats are more likely to produce LTP.     

Layer variations of long-term depression in rat visual cortex

In vitro long-term depression (LTD) is thought to be a model for the loss of cortical responsiveness to an eye deprived of vision during the critical period. Using whole cell recording, the present study investigates the mechanisms of LTD in vitro across layers in developing rat visual cortex. LTD was induced in layers II/III, V, and VI but not layer IV with 10-min 1-Hz stimulation paired with postsynaptic depolarization. LTD in layers II/III and V could be blocked by the N-methyl-D-aspartate (NMDA) receptor antagonist D-aminophosphonovaleric acid (D-AP5) but not by 100 microM (2S)-amino-2-[(1S,2S)-2-carboxycycloprop-1-yl]-3-(xanth-9-yl) propanoic acid (LY341495), a metabotropic glutamate receptor inhibitor. In contrast, LTD in layer VI was blocked by 100 microM LY341495 and (RS)-1-aminoindan-1,5-dicarboxylic acid (AIDA) but not D-AP5 and partially blocked by application of guanosine 5'-O-(2-thiodiphosphate) thilothium salt (GDP-beta-S) in patch pipette, suggesting an involvement of postsynaptic group I metabotropic glutamate receptors (mGluRs). These results indicate that LTD in developing rat visual cortex varies with layer: LTD was absent in layer IV, suggesting a unique plasticity mechanism at geniculocortical synapses; LTD in layers II/III and V depends on NMDA receptors but not mGluRs, and LTD in layer VI requires mGluRs but not NMDA receptors.     

Recovery of cortical binocularity and orientation selectivity after the critical period for ocular dominance plasticity

Cortical binocularity is abolished by monocular deprivation (MD) during a critical period of development lasting from approximately postnatal day (P) 35 to P70 in ferrets. Although this is one of the best-characterized models of neural plasticity and amblyopia, very few studies have examined the requirements for recovery of cortical binocularity and orientation selectivity of deprived eye responses. Recent studies indicating that different mechanisms regulate loss and recovery of binocularity raise the possibility that different sensitive periods characterize loss and recovery of deprived eye responses. In this report, we have examined whether the potential for recovery of binocularity and orientation selectivity is restricted to the critical period. Quantitative single unit recordings revealed recovery of cortical binocularity and full recovery of orientation selectivity of deprived eye responses following prolonged periods of MD (i.e., >3 wk) starting at P49, near the peak of plasticity. Surprisingly, recovery was present when binocular vision was restored after the end of the critical period for ocular dominance plasticity, as late as P83. In contrast, ferrets that had never received visual experience through the deprived eye failed to recover binocularity even though normal binocular vision was restored at P50, halfway through the critical period. Collectively, these results indicate that there is potential for recovery of cortical binocularity and deprived eye orientation selectivity after the end of the critical period for ocular dominance plasticity.     

Induction of NMDA receptor-dependent long-term depression in visual cortex does not require metabotropic glutamate receptors

We tested the role of group I mGluRs in the induction of long-term depression (LTD) in the visual cortex, using the novel mGluR antagonist LY341495 and mice lacking mGluR5, the predominant phosphoinositide (PI)-linked mGluR in the visual cortex. We find that LY341495 is a potent blocker of glutamate-stimulated PI hydrolysis in visual cortical synaptoneurosomes, and that it effectively antagonizes the actions of the mGluR agonist 1S, 3R-aminocyclopentane-1,3-dicarboxylic acid (ACPD) on synaptic transmission in visual cortical slices. However, LY341495 has no effect on the induction of LTD by low-frequency stimulation. Furthermore, mice lacking mGluR5 show normal NMDA receptor-dependent LTD. These results indicate that group I mGluR activation is not required for the induction of NMDA receptor-dependent LTD in the visual cortex.     

Virally mediated knock-down of NR2 subunits ipsilateral to the deprived eye blocks ocular dominance plasticity

NMDA receptors (NMDARs) are important in developmental plasticity in the visual cortex. The NR2A and NR2B subunits of this receptor develop with different time courses, suggesting that they play different roles in plasticity. To understand the role of the NR2B subunit, we knocked-down NR2B gene expression in visual cortex by injecting a recombinant adenovirus containing an antisense NR2B oligonucleotide. To assess knock-down, we injected the recombinant adenovirus into the right visual cortex of rats (p22) or mice (p30). Eight days later we perfused the animals and processed the visual cortex for NMDAR subunit immunoreactivity (IR). NR2B-IR was depleted dramatically in the neuropil near the injection. Depletion was more modest in the neuronal somata. Surprisingly, NR2A-IR was also reduced, but NR1-IR was not reduced. To assess the functional effects of depletion, we measured ocular dominance plasticity with monocular deprivation (MD). We compared mice receiving the NR2B antisense virus with mice receiving virus containing only the GFP sequence and mice receiving no injection. All injections were between p26 and p29 in the right cortex and bilateral recordings were performed 6–8 days later. Animals receiving the antisense virus lost plasticity if the right eye was deprived. If the left eye was deprived, the cortex was normally plastic bilaterally. Injection of control virus had no effect on plasticity. The data indicate that ocular dominance plasticity requires normal NMDARs in the hemisphere ipsilateral to the deprived eye but not in the hemisphere contralateral to the deprived eye.     

Expression of the transcription factor Zif268 in the visual cortex of monocularly deprived rats: effects of nerve growth factor.

Neurotrophins are known to be involved in experience-dependent plasticity of the visual cortex. Here, we have characterized in detail the effects of intraventricular nerve growth factor infusion in monocularly deprived rats by using immunostaining for the immediate-early gene product Zif268 as a marker of functional activity with cellular resolution. We have taken advantage of the rapid regulation of Zif268 by visual input to reveal the cortical units that are responsive to the deprived eye after a period of monocular deprivation. We found that responses to the deprived eye were significantly preserved in the cortex of monocularly deprived rats infused with nerve growth factor. The effects of nerve growth factor were greater for cortical cells located in deep layers and with more peripheral receptive fields. Results from Zif268 staining correlated very well with those obtained by single-cell recordings from the visual cortex. Our results demonstrate that exogenous nerve growth factor preserves the functional input from the deprived eye, enabling cortical neurons to activate immediate-early gene expression in response to stimulation of the deprived eye. Furthermore, we show that the intraventricular infusion of nerve growth factor differentially affects the ocular dominance of cells at various depths and eccentricities in the developing cortex.     

Experience-dependent modification of mechanisms of long-term depression

Mechanisms of long-term potentiation and depression (LTP and LTD) change considerably during development, but the importance of these changes and the factors that control them is not clear. We found that visual experience triggered a switch in mechanisms of LTD in rat perirhinal cortex, an area critical for visual recognition memory. Thus, changes in synaptic plasticity mechanisms were correlated with the changing physiological demands on the CNS.     

cAMP反应元件结合蛋白(CREB)在单眼剥夺弱视大鼠视皮层中的表达研究

目前已对突触可塑性的基本特性有了相当程度的认识 ,但对其发育中神经元可塑性的内在分子机制尚待进一步阐明。不少研究提示 ,c AMP反应元件结合蛋白 ( CREB)在学习、记忆和长时程增强 ( LTP)过程中参与长时程突触的可塑性调节 ,推测其在视觉系统可塑性中也发挥着重要作用。本研究通过建立幼年大鼠单眼剥夺弱视模型 ,应用免疫组织化学方法 ,对视觉发育关键期末 ( P45 )大鼠和成年 ( P90 )大鼠视皮层中 CREB和 p CREB的免疫反应性进行观察、比较和分析。结果 :视觉发育关键期内进行单眼视觉剥夺对大鼠视皮层内总 CREB的蛋白表达没有产生显著影响 ,而 p CREB在 P45大鼠的剥夺眼对侧视皮层单眼反应区的 / 、 层中的蛋白表达较剥夺眼同侧视皮层的相应区域弱 ,该差异在该年龄大鼠的双眼反应区及成年后大鼠视皮层内不存在。结论 :CREB可能通过该磷酸化形式在视觉系统可塑性中发挥作用     

Long-term potentiation and depression in the cerebral neocortex

Long-term potentiation of synaptic efficacy following tetanic synaptic inputs was described originally in the hippocampus, and it has been studied extensively based on the hypothesis that it represents a synaptic model of learning and memory in the brain. In the cerebral neocortex, studies on LTP have burgeoned later, and have progressed less rapidly than those in the hippocampus. Recently, however, experimental data describing the phenomenology and the mechanisms underlying LTP have accumulated in the neocortex, particularly in the visual, somatosensory, and motor cortices. In the developing visual cortex, LTP has been induced by afferent tetanic stimulation at relatively low frequencies, for long duration. Thus, particular attention has been given to parameters of the tetanus optimal for the induction of cortical LTP, and the differences between these and those effective in inducing hippocampal LTP have been reviewed. In the motor cortex, the associative LTP following combined activation of separate sites as well as homosynaptic LTP following activation of single pathways have been reported and these types of synaptic plasticity have been suggested as being a basis for a certain type of motor learning. Long-lasting depression (LTD) of synaptic efficacy also has been reported in the developing visual cortex and suggested as a neural basis for experience-dependent modifications of visual cortical neurons. LTD has been found in other areas of the neocortex as well, although the probability of its induction is relatively low and its functional significance is not yet clear. Among the possible mechanisms for the induction of LTP and LTD, those including the involvement of NMDA receptors, protein kinase C, Ca2+/calmodulin-dependent kinase II, and membrane-associated cytoskeletal proteins have been reviewed, although the results obtained so far are only fragmentary and are premature for definitive conclusions to be drawn.     

Short‐term monocular deprivation alters early components of visual evoked potentials

Key points

• Short‐term monocular deprivation in adult humans produces a perceptual boost of the deprived eye reflecting homeostatic plasticity.
• Visual evoked potentials (VEPs) to transient stimuli change after 150 min of monocular deprivation in adult humans.
• The amplitude of the C1 component of the VEP at a latency of about 100 ms increases for the deprived eye and decreases for the non‐deprived eye after deprivation, the two effects being highly negatively correlated.
• Similarly, the evoked alpha rhythm increases after deprivation for the deprived eye and decreases for the non‐deprived eye.
• The data demonstrate that primary visual cortex excitability is altered by a short period of monocular deprivation, reflecting homeostatic plasticity.

Abstract

Very little is known about plasticity in the adult visual cortex. In recent years psychophysical studies have shown that short‐term monocular deprivation alters visual perception in adult humans. Specifically, after 150 min of monocular deprivation the deprived eye strongly dominates the dynamics of binocular rivalry, reflecting homeostatic plasticity. Here we investigate the neural mechanisms underlying this form of short‐term visual cortical plasticity by measuring visual evoked potentials (VEPs) on the scalp of adult humans during monocular stimulation before and after 150 min of monocular deprivation. We found that monocular deprivation had opposite effects on the amplitude of the earliest component of the VEP (C1) for the deprived and non‐deprived eye stimulation. C1 amplitude increased (+66%) for the deprived eye, while it decreased (−29%) for the non‐deprived eye. Source localization analysis confirmed that the C1 originates in the primary visual cortex. We further report that following monocular deprivation, the amplitude of the peak of the evoked alpha spectrum increased on average by 23% for the deprived eye and decreased on average by 10% for the non‐deprived eye, indicating a change in cortical excitability. These results indicate that a brief period of monocular deprivation alters interocular balance in the primary visual cortex of adult humans by both boosting the activity of the deprived eye and reducing the activity of the non‐deprived eye. This indicates a high level of residual homeostatic plasticity in the adult human primary visual cortex, probably mediated by a change in cortical excitability.

Abbreviations

EEG

electroencephalography

ERP

event related potential

TMS

transcranial magnetic stimulation

VEP

visual evoked potential

     

Differential regulation of synapsin phosphorylation by monocular deprivation in juveniles and adults

The rodent visual cortex retains significant ocular dominance plasticity beyond the traditional postnatal critical period. However, the intracellular mechanisms that underlie the cortical response to monocular deprivation are predicted to be different in juveniles and adults. Here we show monocular deprivation in adult, but not juvenile rats, induced an increase in the phosphorylation of the prominent presynaptic effecter protein synapsin at two key sites known to regulate synapsin function. Monocular deprivation in adults induced an increase in synapsin phosphorylation at the PKA consensus site (site 1) and the CaMKII consensus site (site 3) in the visual cortex ipsilateral to the deprived eye, which is dominated by non-deprived eye input. The increase in synapsin phosphorylation was observed in total cortical homogenate, but not synaptoneurosomes, suggesting that the pool of synapsin targeted by monocular deprivation in adults does not co-fractionate with excitatory synapses. Phosphorylation of sites 1 and 3 stimulates the release of synaptic vesicles from a reserve pool and increases in the probability of evoked neurotransmitter release, which may contribute to the strengthening of the non-deprived input characteristic of ocular dominance plasticity in adults.     

A new form of synaptic plasticity is transiently expressed in the developing rat visual cortex: a modulatory role for visual experience and brain-derived neurotrophic factor.

Synaptic plasticity has been implicated in the mechanisms contributing to the shaping of the cortical circuits responsible for the transmission of the visual input in the rat primary visual cortex. However, the degree of plasticity of the thalamocortical synapse may change during development, perhaps reflecting the degree of stabilization of the circuitry subserving it. We have chosen the ability of this synapse to be first depressed and then potentiated as a specific indicator of its plasticity. In this study we have investigated how this parameter changes during development and the factors controlling it. Extracellular field potentials in cortical layers 2/3 were evoked by stimulation of the white matter in rat primary visual cortex slices prepared at different postnatal ages. Low-frequency stimulation (900 pulses at 1 Hz) of the white matter was used to induce long-term depression of field potential amplitude, whereas long-term potentiation was evoked by high-frequency stimulation consisting of three trains at 100 Hz. We provide evidence that while it is possible to potentiate previously depressed synapses soon after eye opening (postnatal day 17) this synaptic characteristic decreases rapidly thereafter. The decrease in this form of cortical synaptic plasticity closely matches the stabilization of the cortical circuitry towards an adult pattern of connectivity and function. Depressed cortical synapses cannot be potentiated in normal rats at postnatal 23, but they can be potentiated in rats reared in the dark from postnatal days 17 to 29. Moreover, application of brain-derived neurotrophic factor, known to be expressed in an activity-dependent manner, was able to restore the ability of synapses to be potentiated after long-term depression, thus indicating its important modulatory role in brain development.     

Layer 2/3 synapses in monocular and binocular regions of tree shrew visual cortex express mAChR-dependent long-term depression and long-term potentiation

Acetylcholine is an important modulator of synaptic efficacy and is required for learning and memory tasks involving the visual cortex. In rodent visual cortex, activation of muscarinic acetylcholine receptors (mAChRs) induces a persistent long-term depression (LTD) of transmission at synapses recorded in layer 2/3 of acute slices. Although the rodent studies expand our knowledge of how the cholinergic system modulates synaptic function underlying learning and memory, they are not easily extrapolated to more complex visual systems. Here we used tree shrews for their similarities to primates, including a visual cortex with separate, defined regions of monocular and binocular innervation, to determine whether mAChR activation induces long-term plasticity. We find that the cholinergic agonist carbachol (CCh) not only induces long-term plasticity, but the direction of the plasticity depends on the subregion. In the monocular region, CCh application induces LTD of the postsynaptic potential recorded in layer 2/3 that requires activation of m3 mAChRs and a signaling cascade that includes activation of extracellular signal-regulated kinase (ERK) 1/2. In contrast, layer 2/3 postsynaptic potentials recorded in the binocular region express long-term potentiation (LTP) following CCh application that requires activation of m1 mAChRs and phospholipase C. Our results show that activation of mAChRs induces long-term plasticity at excitatory synapses in tree shrew visual cortex. However, depending on the ocular inputs to that region, variation exists as to the direction of plasticity, as well as to the specific mAChR and signaling mechanisms that are required.     

Postsynaptic endocannabinoid release is critical to long-term depression in the striatum

The striatum functions critically in movement control and habit formation. The development and function of cortical input to the striatum are thought to be regulated by activity-dependent plasticity of corticostriatal glutamatergic synapses. Here we show that the induction of a form of striatal synaptic plasticity, long-term depression (LTD), is dependent on activation of the CB1 cannabinoid receptor. LTD was facilitated by blocking cellular endocannabinoid uptake, and postsynaptic loading of anandamide (AEA) produced presynaptic depression. The endocannabinoid necessary for striatal LTD is thus likely to be released postsynaptically as a retrograde messenger. These findings demonstrate a new role for endocannabinoids in the induction of long-term synaptic plasticity in a circuit necessary for habit formation and motor control.     

Age-dependent decline in supragranular long-term synaptic plasticity by increased inhibition during the critical period in the rat primary visual cortex

Supragranular long-term potentiation (LTP) and depression (LTD) are continuously induced in the pathway from layer 4 during the critical period in the rodent primary visual cortex, which limits the use of supragranular long-term synaptic plasticity as a synaptic model for the mechanism of ocular dominance (OD) plasticity. The results of the present study demonstrate that the pulse duration of extracellular stimulation to evoke a field potential (FP) is critical to induction of LTP and LTD in this pathway. LTP and LTD were induced in the pathway from layer 4 to layer 2/3 in slices from 3-wk-old rats when FPs were evoked by 0.1- and 0.2-ms pulses. LTP and LTD were induced in slices from 5-wk-old rats when evoked by stimulation with a 0.2-ms pulse but not by stimulation with a 0.1-ms pulse. Both the inhibitory component of FP and the inhibitory/excitatory postsynaptic potential amplitude ratio evoked by stimulation with a 0.1-ms pulse were greater than the values elicited by a 0.2-ms pulse. Stimulation with a 0.1-ms pulse at various intensities that showed the similar inhibitory FP component with the 0.2-ms pulse induced both LTD and LTP in 5-wk-old rats. Thus extracellular stimulation with shorter-duration pulses at higher intensity resulted in greater inhibition than that observed with longer-duration pulses at low intensity. This increased inhibition might be involved in the age-dependent decline of synaptic plasticity during the critical period. These results provide an alternative synaptic model for the mechanism of OD plasticity.